product name Bestatin
Description: Bestatin (also called Ubenimex) is a potent aminopeptidase-B and leukotriene (LT) A4 hydrolase inhibitor, it is used in the treatment of acute myelocytic leukemia. Bestatin is isolated from the culture filtrate of Streptomyces olivoreticuli MD976-C7. The structure of bestatin was elucidated to be (2S, 3R)-3-amino-2-hydroxy-4- phenylbutanoyll-(S)-leucine. Bestatin itself was not hydrolyzed by either of the enzymes, when bestatin was incubated as substrate, L-leucine was not detected by thin-layer chromatography. Bestatin inhibits proliferation of all the human leukemic cell lines except KG1. Bestatin induces DNA fragmentation quantitatively and DNA ladder and enhances caspase-3 activity in U937 cells. Bestatin dose-dependently induces DNA fragmentation in human leukemic cell lines.
References: Leukemia. 1999 May;13(5):729-34; Clin Exp Metastasis. 1992 Jan;10(1):49-59; Cancer Lett. 2004 Dec 8;216(1):35-42.
308.37
Formula
C16H24N2O4
CAS No.
58970-76-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 2.6mg/mL
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
Ubenimex
other peoduct :
| In Vitro |
In vitro activity: Bestatin inhibits proliferation of all the human leukemic cell lines except KG1. Bestatin induces DNA fragmentation quantitatively and DNA ladder and enhances caspase-3 activity in U937 cells. Bestatin dose-dependently induces DNA fragmentation in human leukemic cell lines. Bestatin dose-dependently inhibits the invasion of SN12M cells into reconstituted basement membrane (Matrigel). Bestatin inhibits the degradation of type IV collagen by tumor cells, but not by tumor-conditioned medium (TCM), in a concentration-dependent manner. Bestatin inhibits hydrolysing activities towards substrates of aminopeptidases in SN12M cells. Bestatin inhibits the tube-like formation of human umbilical vein endothelial cells (HUVECs) in vitro. Bestatin exerts a direct stimulating effect on lymphocytes (and monocytes) via its fixation on cell surface leucine-aminopeptidase, and an indirect effect on monocytes (and lymphocytes) via aminopeptidase B inhibition of tuftsin catabolism. Kinase Assay: Cell Assay: To determine the interaction and the possible role of APN in MDR, RT–PCR was performed to detect the mRNA levels of APN and MDR1 in K562 and K562/ADR cells. After incubation with various concentration of bestatin for 24 h, the expression of APN mRNA was almost unchanged in K562 and K562/ADR cells. However, K562/ADR cells exhibited a significant lower level of APN mRNA than K562 cells. On the other hand, high dose of bestatin (100 μM) induced MDR1 upregulation by 49.4% and 18.0% in K562 and K562/ADR cells, respectively. The result confirmed that bestatin was a substrate of P-gp in mRNA level. |
|---|---|
| In Vivo | Bestatin significantly inhibits the melanoma cell-induced angiogenesis in a mouse dorsal air sac assay. Bestatin reduces the number of vessels oriented towards the established primary tumor mass on the dorsal side of mice implantated of B16-BL6 melanoma cells. Bestatin statistically significantly inhibits leukotriene B4 biosynthesis in the esophageal tissues of EGDA rats and reduces the incidence of EAC in the EGDA rats from 57.7% (15 of 26 rats) to 26.1% (6 of 23 rats). |
| Animal model | 4 mg/kg, dis-solved in normal saline; oral gavage |
| Formulation & Dosage | |
| References | Leukemia. 1999 May;13(5):729-34; Clin Exp Metastasis. 1992 Jan;10(1):49-59; Cancer Lett. 2004 Dec 8;216(1):35-42. |
